Duffy-blood-group-negative human erythrocytes, FyFy, are resistant to invasion in vitro by Plasmodium knowlesi. The FyFy genotype is found predominantly in African and American blacks, who are the only groups completely resistant to infection by P. vivax. To determine if the FyFy genotype is the vivax resistance factor, we performed blood typing on 11 black and six white volunteers who had been exposed to the bites of P. vivax-infected mosquitoes. Only the five FyFy blacks were resistant to erythrocytic infection; the remaining six blacks and all whites had the Duffy-positive determinants (Fya or Fyb or both) and had contracted malaria. We conclude that Duffy determinants (Fya or Fyb or both) on the erythrocyte surface are required for invasion of erythrocytes by vivax merozoites.